The mechanisms underlying central and peripheral nervous system regeneration are poorly understood. As a consequence, no conceptual background to plan interventions exists, and recovery following peripheral nerve injuries remains highly variable and incomplete. Synthetic guidance channels can serve effectively as tools to study the regeneration process and may be utilized clinically in the repair of injured nerves. In the past, synthetic guidance channels have been considered as inert conduits providing axonal guidance, maintaining growth factors, and preventing scar tissue invasion. Little or no emphasis has been placed on the relationship between the physico-chemical properties of the channel and the outcome of regeneration. These relationships must be elucidate since, experimentally, the morphological and functional results of regeneration compare poorly with the normal situation. The guidance channel can be considered as a biomaterial which actively participates in the regeneration process by influencing the cellular and metabolic aspects of regeneration. Three guidance channel characteristics that influence peripheral nervous system (PNS) regeneration have been identified in our laboratory; permeability characteristics of guidance channels directly influence peripheral nerve regeneraton. The permeability characteristics may regulate the movement of nutrients and growth or tropic factors across the channel wall. By varying the molecular weight cut-off of the channel wall and by varying the type of distal tissue inserts it may be possible to identify and separate the importance of extrachannel growth or trophic factors from those originating from the nerve stumps. Use of tubes of the same chemical composition and permeability characteristics but with different inner surface microgeometry resulted in regenerate nervous tissue with varying internal organization. By varying the microgeometry of the inner surface of the guidance channel we hope to better understand the internal organization of the regenerated nervous tissue. Since in vitro neurite outgrowth has been shown to be promoted and directed by electrical activity, guidance channels displaying electrical activities could favor nerve regeneraton in vivo. Guidance channels composed of charged polymers provide an attractive channel material since they preclude the need for an external power source or electrical circuity. In preliminary studies piezolecetric guidance channels significantly enhanced peripheral nerve regeneration compared to non-piezolectric tubes of the same chemical composition. The present proposal focuses on how the magnitude, polarity and pattern of charge generation in piezoelectric channels influence nerve regeneration. The results of the proposed studies may lead to a deeper understanding of regeneration in the PNS and to the development of more efficacious guidance channels.